During the past decade, many nucleoside analogs have been found to the exhibit good antitumor and antiviral activities. Among the presently known synthetic nucleosidic antiviral agents, the more important generally are considered to be 5-iodo-2' -deoxyuridine (IDU), 9-.beta.-D-arabino furanosyladenine (ara-A) and 1-.beta.-D-arabinofuranosylcytosine (ara-C). These compounds, however, are only active against a limited spectrum of viruses which does not include those causing respiratory diseases such as influenza in man. The only nucleosidic analog of which we are aware that is active against these respiratory disease viruses is 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide which is described in U.S. PAT. No. 3,798,209 entitled 1,2,4-Triazole Nucleosides and assigned to the same assignee as this application.
Certain derivatives of this latter compound have also been found to have significant antiviral activity, as have the triazole bases, 1,2,4-triazole-3-carboxamide and 1,2,4-triazole-3thiocarboxamide. Even with the advent of such compounds, however, and the discovery of their antiviral efficacy, there remains a need for compounds which are capable of inhibiting effectively virus infections, especially respiratory disease viruses.
Moreover, when nucleosidic analogs are uses to inhibit either viral or tumor growth, the nucleosides are in vivo metabolized to their corresponding mono or poly phosphates, which are the actual inhibitors of such growth. A major obstacle in the use of nucleoside analogs in chemotherapy, however, is the emergence of cellular resistance to such compounds, as the invasive cells exhibit a low level of kinase or pyrophosphorylase activity and consequently do not produce effective inhibitors. While this problem might be overcome by utilizing nucleoside phosphates, such derivatives often fail to pass through the cellular membrane or are rapidly degraded in the intercellular fluid and thus are ineffective as inhibitors.
In view of the foregoing considerations, it is clearly desirable to have a nucleosidic analog which is capable of effectively inhibiting the development of virus infections and which also possesses superior solubility than presently known antiviral agents. To provide such a compound, however, which not only has acceptable activity but is also capable of penetrating the cellular membrane and contacting the virus infection in effective concentrations, is exceedingly difficult.